Biaryl modification of the 5′-terminus of one strand of a microRNA duplex induces strand specificity

Biaryl modification of the 5′-terminus of one strand of a microRNA duplex induces strand specificity
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DOI:
10.1016/j.bmcl.2010.10.077
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发表时间:
2010-12-15
影响因子:
2.7
通讯作者:
Ueno, Yoshihito
Ueno, Yoshihito
中科院分区:
医学4区
文献类型:
--
作者:
Ogata, Aya;Furukawa, Chihiro;Ueno, Yoshihito

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MicroRNAs (miRNAs)是由20-23个核苷酸组成的单链非编码rna。它们最初作为pri- mirna在细胞核中转录。加工后,一条miRNA双工链(miR-5p/miR-3p双工链)被装载到rna诱导的沉默复合体(RISC)上,产生抑制多个靶基因表达的功能性成熟miRNA。在一些mirna的情况下,两条链都可以作为单链平等地纳入RISC,两条链都可以作为成熟的mirna发挥作用。因此,需要一种选择性表达miR-5p和miR-3p链的技术来识别mirna的不同靶点。在这篇文章中,我们报道了在一条链的5'端携带联芳基单位的miRNA双链的合成和性质。我们发现,在一条miRNA双链的5'端掺入联芳基单位会诱导这些双链的特异性。此外,我们成功地通过使用双芳基修饰的miRNA双链确定了双链的内源性mRNA靶点。(C) 2010 Elsevier Ltd.版权所有。
MicroRNAs (miRNAs) are single-stranded non-coding RNAs composed of 20-23 nucleotides. They are initially transcribed in the nucleus as pri-miRNAs. After processing, one strand from the miRNA duplex (miR-5p/miR-3p duplex) is loaded onto the RNA-induced silencing complex (RISC) to produce a functional, mature miRNA that inhibits the expression of multiple target genes. In the case of some miRNAs, both strands can be equally incorporated into the RISC as single strands, and both strands can function as mature miRNAs. Thus, a technique for selective expression of miR-5p and miR-3p strands is required to identify distinct targets of miRNAs. In this Letter, we report the synthesis and properties of miRNA duplexes carrying biaryl units at the 5'-terminus of one strand. We found that incorporation of biaryl units at the 5'-terminus of one strand of miRNA duplexes induced strand specificity in these duplexes. Further, we succeeded in identifying endogenous mRNA targets for each strand of the duplex by using the biaryl-modified miRNA duplexes. (C) 2010 Elsevier Ltd. All rights reserved.